Molecular docking of fisetin as a multi-target drug in the treatment of Parkinson’s disease

  • Rajendran Malathi Department of Biochemistry, Research and Development Centre, Bharathiar University, Coimbatore - 641046, Tamil Nadu, India,
  • K Prashanthi Department of Biochemistry, Indian Academy Degree College Autonomous, Bengaluru - 560043, Karnataka, India,
  • J. Karthikeyan Department of Biochemistry, Kongunadu Arts and Science College Autonomous, Coimbatore, Tamil Nadu, India
DOI https://doi.org/10.22270/jddt.v9i1-s.2232

Abstract

Fisetin is found in various fruits and vegetables. It is reported to have neurotropic, anti-inflammatory, anti-carcinogenic and also other health benefits. Fisetin has been proved to have neuroprotective effect against Parkinson’s disease (PD).  Elucidation of the molecular interaction of fisetin with various anti-parkinsonian drug targets leads to better understanding mode of action of the drug. The present study is aimed to study the molecular interaction of fisetin with molecular targets having potential role in PD. The molecular properties and drug likeness model score were first analysed for flavonoid fisetin, which was found to be 0.76. The structures of the molecular drug targets, such as MAO A (2BXR), MAO B (2BYB), COMT (2AVD) and tyrosine hydroxylase (2XSN), was extracted from RCSB-Protein Data Bank. Molecular docking was performed using AUTO DOCK-4.2. The docking scores were evaluated by analyzing the minimum binding energy for the first five runs for all the target proteins. The minimum binding energy for MAO A (2BXR), MAO B (2BYB), COMT (2AVD), tyrosine hydroxylase (2XSN) were -10.22 kcal/mol, -9.68 kcal/mol, -7.45 kcal/mol and -6.67 kcal/mol respectively. Out of the 4 potential PD drug targets, MAO A and MAO, genes responsible for oxidative deamination of dopamine, are predicted to have the least minimum binding energy and best interaction with fisetin.


Keywords: Fisetin, docking, multidrug targets, autodock, MAO A, MAO B, COMT, Tyrosine hydroxylase

Downloads

Download data is not yet available.

Author Biographies

Rajendran Malathi, Department of Biochemistry, Research and Development Centre, Bharathiar University, Coimbatore - 641046, Tamil Nadu, India,

Department of Biochemistry, Research and Development Centre, Bharathiar University, Coimbatore - 641046, Tamil Nadu, India,

K Prashanthi, Department of Biochemistry, Indian Academy Degree College Autonomous, Bengaluru - 560043, Karnataka, India,

Department of Biochemistry, Indian Academy Degree College Autonomous, Bengaluru - 560043, Karnataka, India,

J. Karthikeyan, Department of Biochemistry, Kongunadu Arts and Science College Autonomous, Coimbatore, Tamil Nadu, India

Department of Biochemistry, Kongunadu Arts and Science College Autonomous, Coimbatore, Tamil Nadu, India

References

1. Soto C. Unfolding the role of protein misfolding in neurodegenerative diseases. Nat Rev Neurosci 2003; 4:49-60.
2. Hardy J, Orr H. The genetics of neurodegenerative diseases. J Neurochem 2006; 97:1690-9.
3. Manoharan S, Guillemin GJ, Abiramasundari RS, Essa MM, Akbar M, Akbar MD. The role of reactive oxygen species in the pathogenesis of Alzheimer's disease, Parkinson's disease, and Huntington's disease: a mini review. Oxid Med Cell Longevity 2016. DOI:10.1155/2016/8590578
4. Sonia Angeline M, Sarkar A, Anand K, Ambasta RK, Kumar P. Sesamol and naringenin reverse the effect of rotenone-induced PD rat model. Neuroscience 2013; 254:379-94.
5. Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinson's disease. J Parkinson’s Disease 2013; 3:461–91.
6. Benavente-García, O.; Castilho, J. Update on Uses and Properties of Citrus Flavonoids: New Findings in Anticancer, Cardiovascular, and Anti-inflammatory Activity. J. Agric. Food Chem., 2008, 56:6185–6205.
7. Naeimia AF, Alizadeh M. Antioxidant properties of the flavonoid fisetin: An updated review of in vivo and in vitro studies. Trends in Food Science & Technology 2017; 70:34-44.
8. William Dauer and Serge Przedborski. Parkinson’s Disease: Mechanisms and models Neuron. 2003; 39:889-909.
9. Morris GM, Goodsell DS, Pique ME, et al. Auto dock4 and AutoDockTools4 automated docking with selective receptor flexibility. J Comput Chem 2009; 16:2785–91.
10. Morris GM, Goodsell DS, Halliday RS, et al. Automated docking using a lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 1998; 19:1639–62.
11. Pettersen EF, Goddard TD, Huang CC. et al UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem 2004; 25(13):1605-12.
Crossmark
Statistics
996 Views | 867 Downloads
How to Cite
1.
Malathi R, Prashanthi K, Karthikeyan J. Molecular docking of fisetin as a multi-target drug in the treatment of Parkinson’s disease. JDDT [Internet]. 15Feb.2019 [cited 17May2024];9(1-s):1-. Available from: https://jddtonline.info/index.php/jddt/article/view/2232
Issue
Vol 9 No 1-s (2019): Volume 9, Issue 1-s Jan-Feb 2019
Section
Research
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Authors who publish with this journal agree to the following terms:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).